Certain di-halo-s-triazines used as plant fungicides

ABSTRACT

2-(HETEROARYL SUBSTITUTED)-4,6-DI-HALO - S - TRIAZINES ARE USEFUL AS PESSTICIDES BEING TERIA, VIRUSES AND INSECTS WHICH ATTACK PLANTS.

United States Patent Office Patented Aug. 20, 1974 US. Cl. 424-249 5Claims ABSTRACT OF THE DISCLOSURE 2- (Heteroarylsubstituted)-4,6-di-halo s triazines are useful as pesticides, beingactive in controlling fungi, bacteria, viruses and insects which attackplants.

This is a division of application Ser. No. 133,702, filed 13, 1971, nowPat. No. 3,681,332, dated Aug. 1,

This invention relates to certain di-halo-s-triazine derivatives whichare useful as plant pesticides, to pesticidal compositions containingsaid derivatives and to their use in protecting economically importantplant life from attack by pests. By the term pests as used herein, wemean to include fungi, bacteria, viruses, insects and the like whichcause destruction or deterioration of valuable plant life whilst theterm pesticide is intended to embrace partial and total eradication ofsuch pests as well as prevention of attack by such pests.

According therefore to a first aspect of the present invention, there isprovided a method of treating plants susceptible to attack by pestswhich comprises applying to said plants a pesticidal amount of adi-halo-s-triazine of the formula:

t t N N wherein X is halogen, preferably chlorine or bromine, and R is amonoor bi-cyclic heteroaromatic group linked through a carbon atom tothe triazine ring, said group being selected from thienyl, furyl,pyrrolyl, benzothienyl, benzofuryl and indolyl and being optionallysubstituted by one or more lower alkyl, lower alkenyl,hydroxy(lower)alkyl, carboxy(lower)alkyl, lower alkoxy, lower acyl,phenyl, phenyl(lower)alkyl, nitro, amino, halogen or, in the case wherethe heteroaromatic group is thienyl, by a 2-chloro-4-thienylsubstituent.

The term lower in qualifying various groups is used herein to mean thosegroups containing up to 6 carbon atoms.

In accordance with a feature of the present invention, a sub-genus ofcompounds of formula I which is preferred for use in the presentinvention is the group in which R is selected from the followingstructures:

wherein R is hydrogen, C, alkyl, vinyl, allyl, hydroxymethyl,hydroxyethyl, carboxymethyl, carboxyethyl, phenyl, benzyl or phenethyland R is hydrogen, C, alkyl, C alkoxy, C, acyl, phenyl, nitro, amino,chlorine or bromine. Within that sub-genus, the compounds in which R isan optionally substituted pyrrolyl or indolyl group are especiallyvaluable for their broad-spectrum fungicidal and bactericidal action.

In carrying out the method of the present invention, the compounds offormula I may be applied to the foliage of crops and plants and/or tothe soil or water in which the crops or plants are growing. Thecompounds will normally be applied in the form of pesticidalcompositions.

According therefore to a second aspect of the present invention, thereis provided a pesticidal composition comprising the active ingredientsin association with a nonphytotoxic diluent or carrier material and aprocess for preparing such pesticidal compositions comprising mixing apesticidally-active ingredient of formula I with said diluent or carriermaterial. The latter may be, for example, one or more of water,alcohols, glycols, glycolethers, petroleum distillates and variousdispersion media such as surfactants, emulsifiers and finely dividedinert solids. The concentration of the di-halo-s-triazines in thesecompositions will vary depending on whether the composition is to beused directly as a dust or is intended as an emulsifiable concentrate orwettable powder designed to be subsequently diluted for example withwater prior to use.

It will of course be appreciated that in the case of compositionscomprising an active ingredient of formula I which is a known compound,we do not include within the composition aspect of the invention meresolutions of the active ingredient in water alone or in the commonrecrystallisation media such as dioxan/water or ethanol/ water. However,such solutions, when also containing emulsifying agents or otheradditives such as antifoaming agents or thickening agents, do form aspart of this invention, as do the concentrate compositions hereinafterdescribed.

Since in use the compounds will normally be applied to infected orsusceptible plants as compositions containing from about 5 to 2000 ppm,preferably from about 200 to 1000 p.p.m., of the active ingredient, itis normally convenient for ease of formulation, storage, package, etc.,to formulate the active ingredient as a liquid or solid concentratecomposition.

Liquid concentrates may be prepared by dissolving, dispersing orsuspending from 0.1 to 30% of the active ingredient in water or asuitable water-miscible solvent such as, for example, suitable aromatic,aliphatic or cycloaliphatic hydrocarbons, ketones or alcohols to whichmay be added an emulsifying agent, for example a nonionic or ionic typeor blend such as condensation products or alkylene oxides with phenolsand organic acids, polyoxyethylene derivatives or sorbitan esters,complex etheralcohols and the like.

Solid concentrate mixtures may be prepared by inc0rp0- rating from 5 toof the di-halo-s-triazine derivative in a finely divided solid carriersuch as bentonite, fullers earth, diatomaceous earth, hydrated silica,diatomaceous silica, kaolin, expanded mica, at-tapulgite, talc, chalkand the like. Such concentrates may be formulated for direct use or may,if desired, be diluted with additional inert solid carriers to producedusting powders. Alternatively dispersing and/or wetting agents may beincorporated to form wettable powder concentrates which subsequently maybe dispersed in water or in other aqueous carriers to form spraycompositions. Suitable wetting and emulsifying agents include sodiumlauryl sulphate, sodium lignosulphate and other suitable nonionic andanionic surfactants or blends thereof.

The di-halo-s-triazine derivatives of the invention may also beincorporated in tablets, pellets, capsules or formulated as aerosols orsprays to ensure that the pesticidal action can be obtained at the locusof the disease.

The compounds of formula I have, as stated earlier, been found to beuseful as pesticides. In particular, the compounds of the presentinvention have shown activity against various phytopathogenic fungi suchas Alternaria tenuis, Batrytis cinerea, B. viticola, Colletotrichumatramentarium, C. cofieanum, C. lagenarium, Penicillium expansum,Peronospora sp., Piricularia oryzae, Phytophthora imfestans, Uromycesappendiculatus and Venturia sp. The compounds are also active for thecontrol of Maize dwarf mosaic virus, Bean mosaic virus, bacterialblight, bacterial wilt, Crown gall as well as being useful asinsecticides, in particular giving good contact control of 2-SpottedSpider Mite.

The fungicidal action of the di-halo-s-triazines of the presentinvention may be demonstrated by reference to the test results set outin Table I below, these results being obtained with representativecompounds of the invention in standard foliar fungicide tests. As shown,the compounds display significant fungicidal activity against thediseases tomato late blight, anthracnose of cucumber, rice blast,Helminthosporum leaf spot of barley and grey mould of grapes.

The test procedures used are described in the following paragraphs. Ineach test, the compound Was formulated as an emulsion or solution at aconcentration of 400 ppm. and applied as a spray.

Rice blast.--The aqueous emulsion of the test compound was applied toall leaf surfaces of 14-day-old rice plants of the NATO variety andallowed to dry. The foliage was then inoculated with a water suspensionof conidia (Piricularia oryzae race N-1) by means of a sprayer. Thetreated plants were placed in a moist chamher at 65 F. for 40 hoursbefore being returned to the greenhouse. Eight days thereafter, thesymptoms of the blast disease were observed and compared with controlplants.

Cucumber anthracnose.-The aqueous emulsion of the test compound wassprayed on all leaf surfaces of 15- day-old cucumber plants (GreenProlific variety) and allowed to dry. The foliage was then inoculatedwith a water suspension of conidia (Collectotrichum lagenarium) by meansof a sprayer.

Following inoculation, the treated plants were placed in a moist chambermaintained at 75 F. for 40 hours after which the plants were returned tothe greenhouse. On the 10th day following treatment and inoculation thedisease symptoms were observed and recorded and compared with controlplants.

Tomato late blight.The aqueous emulsion of the test compound was sprayedon all leaf surfaces of 28-day-old tomato plants of the Bonnie Bestvariety and allowed to dry. The plants were then inoculated With a watersuspension of fungal propagules (Phytopththora infestans) by means of asprayer. The plants Were placed in a moist chamber maintained at atemperature of 65 F. for 24 hours after which they were returned to thegreenhouse. Three days thereafter, the symptoms of late blight diseasewere observed and recorded and compared with control plants.

Helminthosporum leaf spot of barley.The aqueous emulsion of the testcompound was sprayed on 6-day-old barley seedlings 4-5 inches tall ofthe Larker variety and allowed to dry. The plants were then inoculatedwith an aqueous suspension of spores of Helminthosporum sativum andplaced in a moist chamber at 65 F. for 48 hours. Two days later theplants were removed from the chamber and placed in the greenhouse. Fourdays thereafter, or 12 days from planting, the symptoms of leaf spotdisease were observed and recorded and the results were compared withcontrol plants.

Grey mould of grapes.Grape clusters (four berries per cluster) of RedEmperor grapes were sterilised with a 1.5% solution of sodiumhypochlorite, rinsed with distilled Water and allowed to dry. Theclusters were then burnt out in alcohol to ensure complete sterilisationand to predispose the berries to infection. The test compound was thenapplied by spray as a 1% solution in acetone/ ethanol and the berriesdried. A spore suspension of Batrytis cinerea was then applied evenlyover the clusters and after 48 hours incubation at 75 F., the diseasesymptoms were noted and compared with controls.

TABLE I Compound F TF N N 2|: Plant disease activity Late Anthrac- RiceLeaf Grey R X blight; nose blast spot mould P Cl 4+ 5 4+ 1 5 F Br 3 4+4+ 1 Fr- Cl 1 3 3 1 2 O;N Cl 3 H3OL Cl 5 l5 5 5 H5Cz W 01 3 1 OzN LS Inthe above Table, activity ratings have the following meaning:

-= Not tested 1=No control 2=Slight control 3 =Moderate control 4: Goodcontrol 5 :Complete control.

The compounds of formula I above in Which R is thienyl or furyl havebeen generally described in US. Patent Specificaiton No. 3,407,201 asintermediates in the preparation of compounds of the formula:

N W-f THalogen X-A II wherein A is an aromatic ring system containing atleast one ring nitrogen atom, X is a divalent hetero-atom bridge memberchosen from -O-, -S, NH and -N lower alkyl-, and W represents inter aliaa monovalent heterocyclic residue linked through a carbon atom with thetriazine ring and containing no more than carbon atoms. The onlyspecific examples given in the specification of W representing such aheterocyclic residue are unsubstituted furyl and thienyl. Although thecompounds of formula II are said to be fungicides and bactericides, nosuch properties are attributed to or even suggested for theintermediates wherein the group XA in formula II is a halogen atom.Indeed it is stated quite categorically in column 3 of the said US.specification that the structural element:

JJKN\ Halogen N A-f THalogen I Halogen III wherein A is a furyl orthienyl residue of formula:

U U4 1 i in which X is oxygen or sulphur and U U and U represent thesame or dilferent hydrogen, C alkyl or phenyl. The hydroxyaryl striazine products disclosed in the French specification are said to beuseful for protecting organic materials against the effects of heat, airand ultraviolet radiation. There is no suggestion in the specificationthat the intermediates of formula IV have any utility other than in thepreparation of the hydroxyaryl end products and in particular there isno disclosure or suggestion that these intermediates possess usefulpesticidal activity as has now been discovered by the applicants.

From the above described prior art, it can be seen that the majority ofthe compounds of formula I above in which R is substituted thienyl orfuryl have not been specifically described or suggested in the prior artand nor has their pesticidal action been envisaged. They are accordinglynoveland non-obvious compounds and form a part of this invention.

According therefore to a third aspect of the present invention, thereare provided novel compounds of the formula N f i N N wherein X is ahalogen atom, preferably chlorine or bromine, and R is a heteroaromaticgroup linked through a carbon atom with the triazine ring, R beingeither:

(a) a substituted furyl group in which at least one substituent isselected from lower alkoxy, lower acyl, nitro, amino or halogen;

( b) a substituted thienyl group in which at least one substituent isselected from lower alkoxy, lower acyl, nitro, amino, halogen, or a2-chloro-4-thienyl group;

(c) a benzothienyl or benzofuryl group optionally substituted by one ormore lower alkyl, lower alkoxy, lower acyl, nitro, amino or halogen; or

(d) a pyrrolyl or indolyl group optionally substituted on the nitrogenby lower alkyl, lower alkenyl, hydroxy (lower)alkyl,carboxy(lower)alkyl, or phenyl(lower) alkyl and optionally substitutedat one or more ring carbon atoms by lower alkyl, lower alkoxy, loweracyl, phenyl, nitro, amino or halogen.

In respect of groups (c) and (d), the aforementioned prior art is, ofcourse, completely silent both as to the generic structures involved andthe species falling within that genus. As mentioned previously,compounds of group ((1) form an especially valuable part of thisinvention in view of their broad-spectrum of activity, in particularthose compounds of formula VI wherein R has the structure:

where R, is hydrogen, methyl, methoxy, acetyl, nitro,

amino, chlorine or bromine, and-R is hydrogen, C

alkyl, vinyl, hydroxyethyl, carboxyethyl, benzyl or phenethyl.

According to a fourth aspect of the present invention, the novelcompounds of this invention may be prepared by a method analogous tothat described in French Specification No. 1,387,435, ie by halogenationof the corresponding dioxo compounds. The latter may be prepared byreacting an appropriate acid derivative of the heteroaromatic compoundof formula R-H with a biguanide to form the corresponding guanaminewhich is hydrolysed by means of an acid to yield the dioxo compound.Alternatively the dioxo compound may be obtained by cyclising under theinfluence of an alkali the appropriate acyl biuret of formulaRCONHCONHCONH the latter being obtained either by direct acylation ofbiuret or by reaction of an acid chloride of formula RCOCl withdicyandiamide followed by acid hydrolysis of the resultant acylcyano-guanidine. Suitable halogenating agents of use for thehalogenation of the dioxo compound include phosphorus pentachloride,phosphorus trichloride, phosphorus tribromide, bromine, phosphorylchloride, phosphoryl bromide, phosphorus tri-iodide and suitablemixtures thereof.

It can be seen that use of the known method requires a time-consuming,multi-stage process to prepare the dioxo intermediates. In accordancetherefore with a fifth aspect of the present invention, theaforementioned multi-stage process may be avoided by the use of a newand improved one-stage synthesis for preparing both the novel and knowncompounds of the invention characterised in that a cyanuric halide isreacted with a heteroaromatic compound of formula R--I-I or a metallatedderivative thereof. Where a non-metallated compound is used, it isnormally desirable to carry out the reaction in the presence of aFriedel-Crafts catalyst such as aluminium chloride. However, where theheteroaromatic compound is an N- substituted pyrrole, no such catalystis necessary since the reaction proceeds smoothly merely by heating thetwo reactants in a suitable solvent such as benzene.

The metallated compounds referred to above may be prepared by reactingthe appropriate heteroaromatic compound with a suitable metallatingagent such as magnesium, a suitable Grignard reagent or an alkyl lithiumcompound. Advantageously the metallated derivative thus prepared isslowly added with stirring to a solution of the cyanuric halide in asuitable solvent at low temperature, preferably between and C.Thereafter stirring is continued usually for from /2 to 4 hours atbetween 0 and 25 C. whereupon the reaction is either complete or iscompleted by refluxing for a short period of up to 3 hours or by leavingthe reaction mixture to stand at about 20 to 25 C. for up to 24 hours.

Where in the above described methods a nitro substituted heteroaromaticgroup is required, this may be obtained by direct nitration of thecorresponding di-halos-triazine and indeed must be so obtained in thecase of the new and improved method of the present invention. In somecases, this nitration may cause hydrolysis to the corresponding dioxocompounds but, as will be appreciated from the above description, thesemay readily be re-halogenated. It will also be apparent that thishydrolysis and re-halogenation provides asimple method of converting onehalogen to another. Thus, for example, a dichloros-triazine may behydrolysed and then brominated using, for example, a mixture ofphosphorus tribromide and bromine to give the correspondingdibromo-s-triazine.

Exemplary of compounds which can be prepared by the foregoing methodsand which are of use as pesticides in accordance with the presentinvention are:

2-( 1 '-phenylpyrrol-2'-y1) -4,6-dichloro-s-triazine 2-'(5'-nitropyrrol-3 '-yl -4,6-dichlor-s-triazine 2 1'-ethylpyrrol-2'-yl-4,6-dibromo-s-triazine 2- (5 '-methoxypyrrol-2'-yl-4,6-dibromo-s-triazine 2 (pyrrol-2'-yl) -4,6-dichloro-s-triazine 2-(4-nitro-5-ethylrhien-2'-yl) -4,6-dici1loro-s-triazine 2- (5-'bromothien-2'-yl) -4,6-dichloro-s-triazine 2- 3'-methylbenzo[b]thien-2'-y1) -4,6-dichloro-s-triazine 2-( thien-2'-yl)-4,6-dichloro-s-triazine 2-( 1',3 -dimethylpyrrol-2'-yl)-4,6-dichloro-s-triazine 2- (thien-3'-yl) -4,6-dichloro-striazine 2-5-nitroindo1-2'-yl) -4,6-dibromo-s-triazine 2- benzo [b] thien-2-yl)-4,6-dibromo-s-triazine 2- 5 '-acetylthien-2'-yl -4,6-dibromo-s-triazine2- benzo [b] thien-3 '-yl -4,6-dibromo-s-triazine 2- 3-methylthien-2'-yl -4,6-dichloro-s-triazine 2- indol-3 '-yl-4,6-dichloro-s-triazine 2- (benzo [b fur-2-yl -4,6-dichloro-s-triazine2- 5 '-nitrofur-2'-yl -4,6-dibromos-triazine 2(1'-allylpyrrol-2'-y1)-4,6-dibromo-s-triazine 2- 5 '-chloropyrrol-3'-yl-4,6-dichloro-s-triazine 2-(1'-methyl-5-nitropyrrol-2'-yl)-4,6-dibromo-s-triazine 2- 5'-nitrothien-3 '-yl) -4,6-dichl0ro-s-triazine 2- 5 '-chloroindol-3 '-yl-4,6-dichloro-s-triazine 2- 5 -ethylbenzo [b] thien-3'-yl)-4,6-dichloro-s-triazine 2- (5 ,6'-dimethylbenzo [b] fur-2-yl-4,6-dichloro-s triazine 2- 5 '-nitrobenzo [b] thien-2-yl)-4,6-dichloro-s-triazine 2- [5 2"-ch1orothien-4"-yl) thien-2'-yl]-4,6-dibromo-striazine 2- 1-phenylindol-3 '-yl )-4,6-dibromo-s-triazine2-( 1-phenethylpyrrol-2-yl -4,6-dichloro-s-triazine 2-(1-n-butylpyrrol-3 '-yl) -4,6-dichloro-s-triazine 2- (4'-bromothien-2-yl-4,6-dichloro-s-triazine 2- 5 '-acetylpyrrol-2'-yl-4,6-dichloro-s-triazine 2-( 1 '-methylpyrrol-2'-yl-4,6-dichloro-s-triazine 2- (pyrrol-3 -yl -4,6-dibromo-s-triazine 2-( l-phenylindol-2'-yl) -4,6-dichloro-s-triazine 2-( 1-t-butylpyrrol-2'-yl-4,6-dichloro-s-triazine 2-( 1-vinylpyrrol-2-yl)-4,6-dichloro-s-triazine 2-(1'-isopropyl-5-nitropyrrol-2'-yl)-4,6-dichloro-striazine 2-1'-;8-hydroxyethylpyrrol-3 '-yl) -4,6-dibromo-s-triazine 2-( 1'-carboxymethylpyrrol-2'-yl -4,fi-dichloro-s-triazine.

The following Examples will further illustrate the preparation of thenovel compounds of this invention:

EXAMPLE 1 2- (5 '-Nitrofur-2'-yl -4,6-dichloro-s-triazir1e 2 (5'Nitrofur 2' yl) 4,6 dioxo s triazine (0.13 g.) was heated under refluxwith PCl (0.3 g.) and POCl (0.6 g.) for 24 hours. The liquid obtainedwas allowed to cool to room temperature, poured onto crushed ice (10 g.)and stirred for 30 minutes. The solid was collected on a filter, driedand extracted into ether. The ether was evaporated off and the solidrecrystallised from carbon tetrachloride: petroleum ether (1:2) to givethe desired product, m.p. 166168 C. The dioxo intermediate was preparedas follows: A mixture of dicyandiamide (22.6 g., 0.27 mole) and KOHpellets (28 g., 0.425 mole) (assay pure) was vigorously stirred inacetone (200 ml.) at 1520 C. for 1 hour and then at 05 C. for anotherhour. To this cold suspension was added dropwise 2-furoyl chloride (27.4g., 0.21 mole) in acetone (50 ml.); the mixture gradually turned thick,more acetone (150 ml.) was added to facilitate stirring for a period of3 hours. The mixture was cooled in the fridge overnight, buff colouredsuspension was diluted with water (750 ml.); clear solution wasacidified with glacial acetic acid (20 ml.), the resulting precipitatewas collected on a filter, washed with water and dried under vacuum (ca.19 g.), which was heated under reflux in water (500 ml.) containingcone. HCl (25 ml.) for 1 hour and left overnight; the needle shapedcrystals separated, were collected on a filter, washed with cold waterand dried under vacuum, crystallised from water, m.p. 204-206 C., yield16 g. The crystalline solid (12.5 g.) was heated at 60-65 C. 1n water(200 ml.) containing KOH (16 g.) for 16 hours. When cold, the solutionwas filtered and acidified with glacial acetic acid (20 ml.), theresulting white precipitate cooled in the fridge, and then collected ona filter, washed with 5% aqueous acetic acid ml.), water (400 ml.) anddried under vacuum, 9 g.; crystallised from water, m.p. 300 C.

Analysis: C H N O Found (percent): C, 46.21; H, 23.28. Requires(percent): C, 46.91; H, 2.81;

The above compound (5 g.) was heated under reflux with PCl (11.5 g.) andPOCl (30 ml.) for 3 hours, the mixture, on cooling, was poured ontocrushed ice (400 g.) and stirred for 30 minutes; the light brown solidwas filtered, washed with water and dried, ca. 4.7 g. recrystallisedfrom acetone, m.p. 104 C.

Analysis: C H N OCl Found (percent): C, 39.11; H, 1.59; N, 19.63; 0,7.65; CI, 32.58. Requires (percent): C, 38.92; H, 1.40; N, 19.44; 0,7.41; CI, 32.82.

The resultant 2 (fur 2' yl) 4,6 dichloro s triazine (0.5 g.) was addedportionwise to a mixture of 3:1 cone. H 50 and cone. HNO (3 ml.) at -5?0, the reaction mixture was stirred for minutes and poured onto crushedice g.), yielding 2 (5-nitrofur 2' yl)- 4,6 dioxo s triazine, which wasfiltered and dried in vacuum, 0.13 g. This product may also be obtainedby hydrolysis of the dichloro compound under reflux with ethanol andconcentrated sulphuric acid, followed by nitration of the resultant2-(fur-2'-yl)-4,6-dioxo-s-triazine.

EXAMPLE 2 2- 4-Nitrothien-2'-yl -4,6-dichloro-s-triazine 2 (4'Nitrothien 2 yl) 4,6 dioxo s triazine (0.5 g.) was chlorinated by themethod of Example 1 to yield the desired product, m.p. 186-187 C. afterrecrystallisation from 10:1 hexanezchloroform mixture. The dioxointermediate was prepared as follows:

A solution of sodium methoxide, prepared from Na (1.0 g., 0.04 g. atoms)in absolute methanol (20 ml.) was added to a suspension of biguanidesulphate (6.2 g., 0.02 mole) in methanol (30 ml.) followed by ethyl4-nitrothien-2-yl-carboxylate (4.02 g., 0.02 mole) with stirring; themixture was kept stirring for 48 hours, diluted with water, solidfiltered, washed with water and dried under vacuum at 110 C.; 4.8 g.,crystallised from dimethyl formamide to give 2 (4' nitrothien 2' yl)-4,6-diamino-s-triazine. This, on hydrolysis with 90% H SO afforded thecorresponding dioxo intermediate.

EXAMPLE 3 By the method of Example 1, the following compounds of theinvention were prepared by halogenation of the corresponding dioxocompounds, the latter being themselves prepared either by the methoddescribed in Example 1 or Example 2:

2- (5 '-bromothien-2-yl) -4,6-dichloro-s-triazine,

m.p. 104-106" C. 2-(benzo[b]thien-2-yl)-4,6-dichloro-s-triazine,

m.p. 236238 C. 2- (benzo [b] thien-3 '-yl -4,6-dichloro-s-triazine,

m.p. 198-200 C. 2-( 1'-methylpyrrol-2'-yl) -4,6-dichloro-s-triazine,

m.p. 157 C. 2-(pyrrol2'-yl)-4,6-dichloro-s triazine, m.p. 138-140 C.2-(5'-methoxythien-2'-yl)4,6-dichloro-s-triazine,

m.p. 107 C. 2-(3'-methoxythien-2'-yl)-4,6-dichloro-s-triazine,

m.p. 208-210 C. 2-(5'-acetylthien-2-yl)-4,6-dichloro-s-triazine,

m.p. 152 C. 2- l -ethylpyrrol-2'-yl) -4,6-dichloro-s-triazine,

m.p. 115 C. 2-( 1'-n-butylpyrrol-2'-yl) -4,6-dichloro-s-triazine,

m.p. 44-46 C. 2( 1',5'-dimethylpyrrol-2'-yl)-4,6-dichloro-s-triazine,

m.p. 170 C. 2- 1'-benzylpyrrol-2'-yl) -4,6-dichloro-s-triazine,

m.p. l25-l27 C. 2- 5 -methylpyrrol-2'-yl) -4,6-dichloro-s-triazine,

m.p. 208209 C. 2-(indol-3'-yl)-4,6-dichloro-s-triazine, m.p. 250-252 C.

10 2- (5 '-ethyl-4-nitrothien-2-yl) -4,6-dichloro-s-triazine,

m.p. ISO-155 C. 2-( 1'-methyl-4-nitropyrrol-2'-yl)-4,6-dichloro-s-triazine,

m.p. 179 C. 2-(5'-nitropyrrol-2'-yl)-4,6-dichloro-s-triazine,

m.p. 170-173 c.

EXAMPLE 4 In addition to the methods for obtaining nitrated productsdescribed in Examples 1 and 2, the following method for direct nitrationof a dichloro compound maybe employed with certain compounds of theinvention:

To a suspension of 2-(pyrrol-2'-yl)-4,6-dichloro-s-triazine (2.15 g.) inacetic anhydride (12.5 ml.) cooled in an ice bath, was added dropwisewith stirring a mixture of fuming nitric acid (0.8 g.) in aceticanhydride (2 ml.) at a temperature of 510 C. The mixture was stirred for5 minutes, poured on to crushed ice and extracted with ether. The etherextract afforded a solid (1.8 g.) which on fractional crystallisationfrom carbon tetrachloride yield 2-(5-nitropyrrol 2' yl)4,6-dichloro-s-triazine, m.p. 170-173 C.

The following Examples will illustrate the new method invented by theapplicants for preparing both the novel and known compounds of theinvention.

EXAMPLE 5 2- (5 '-Bromothien-2-y1)-4,6-dichlor0-s-triazine Bromoethane(0.75 ml., 0.01 mole) was added dropwise to a stirred suspension ofmagnesium turnings (12.2 g., 0.05 g. atoms) in dry ether (50 ml.) underreflux. 2,5-Dibromothiophene (10 g., 0.041 mole) in dry ether (200 ml.)was added to the refluxing mixture over a period of 8 hours, addingfurther magnesium (12.2 g., 0.05 g. atoms) in 8 portions. The mixturewas heated under reflux for a further 6 hours then, after cooling, theclear solution was decanted from the excess magnesium and added dropwiseto a stirred solution of cyanuric chloride (3.7 g., 0.02 mole) in drybenzene (50 ml.) at 5. After stirring for 2 hours at room temperatureand 3 hours under reflux the mixture was evaporated to dryness undervacuum and the residue was extracted with petroleum spirit.Chromatography of the extract on a silica gel column, elutiug with amixture of benzene and petroleum spirit (1 :4 by volume) gave, onevaporation of the eluate, a solid, which was crystallised fromacetone-water and then from petroleum spirit to give pale yellowneedles, m.p. 104106 C.

EXAMPLE 6 2- Thien-2-yl -4,6-dichloro-s-triazine 2-Bromothiophene g.,0.61 mole) in dry ether (100 ml.) was added dropwise to a stirredsuspension of magnesium turnings (15.2 g., 0.62 g. atoms) in dry ether(300 ml.) under reflux. The resulting dark solution was cooled and addeddropwise over 30 minutes to a stirred solution or cyanuric chloride(73.6 g., 0.40 mole) in benzene (400 ml.) at O5 C. After stirring for afurther 1 hour at room temperature the mixture was evaporated to adryness under vacuum and the residual brown solid was extracted with hotpetroleum spirit. On cooling, the extract deposited pale yellow crystals(57.5 g.), m.p. C.

EXAMPLE 7 2-(Pyrrol-2'-yl) -4,6-dichloro-s-triazine To a cooled(ice-salt bath) solution of methyl magnesium bromide (0.05 mole) in dryether (40 ml.) was added dropwise with stirring pyrrole (freshlydistilled) (3.4 g., 0.05 mole); the mixture kept stirring for 15 minutesand then gradually added dropwise with stirring to an ice coldsuspension of cyanuric chloride (6.1 g., 0.033 mole) in dry benzene (50ml.) at 05 C. The mixture was stirred at this temperature for 1 hour andthen left at 20-25 C. overnight and finally evaporated under vacuum atordinary room temperature. The solid residue was extracted in a Soxhletapparatus with petroleum ether (GO-80 C.); on evaporation of the solventgreenish crystals appeared, which were recrystallised from petroleumether (6080 C.), ca. 3 g., m.p. 138140 C.

EXAMPLE 8 2- (Thien-3 '-yl) -4,6-dichloro-s-triazine 3-Bromothiophene (5g., 0.0306 mole) in dry ether (35 ml.) was added dropwise to a stirredsolution of n-butyl lithium (15.5 ml. of a 2.25M solution) in n-hexaneat -70 C. under nitrogen cover. After stirring for a further 30 minutesat -70 C. the clear solution was added in small portions to a stirredsolution of cyanuric chloride (5.0 g., 0.027 mole) in dry benzene (50ml.) at C. After stirring for a further 30 minutes at 0 C. and 1 hour atroom temperature, the pale solid was removed by filtration and thefiltrate was evaporated to dryness under vacuum. The residue wasextracted with hot petroleum spirit and the extract was evaporated todryness to give a pale solid which was recrystallised from acetone-waterand then from petroleum spirit. Yield 2.3 g., m.p. 134- 136 C.

EXAMPLE 9 2-(Benzo [b] thien-2-yl)-4,6-dichloro-s-triazineBenzo[b]thiophene (20.1 g., 0.15 mole) in dry ether (100 ml.) was addeddropwise to a stirred solution of n-butyl lithium (75 ml. of a 2Msolution) in n-hexane at 40 C. under nitrogen cover. After 2 /2 hours,the resulting light yellow suspension was added dropwise to a stirredsolution of cyanuric chloride (27.6 g., 0.15 mole) in dry benzene (100ml.) and ether (50 ml.) under nitrogen at 0-5 C. After stirring for 18hours at room temperature, the solvent was removed under vacuum. Theresidue was extracted with hot hexane and sublimed in vacuo to give 0.4g. of the desired product, m.p. 236- 238 C.

EXAMPLE 10 2-(Thien-2-yl)-4,6-dichloro-s-triazine n-Butyl lithium (21.8ml.) of a 2.2M solution in hexane, and dry ether (10 ml.) was addedquickly to a mixture of dry thiophene (4.2 g., 0.05 mole) and dry ether(10 ml.) under nitrogen. The whole was stirred vigorously for 25 minuteswhen butane was freely evolved. The reaction was completed by refluxingwith stirring for a further 90 minutes.

The Z-thienyl lithium was so obtained as a straw coloured slurry. It wascooled in ice-water and then added dropwise to a well-stirred suspensionof cyanuric chloride (9.2 g., 0.05 mole) in dry benzene (25 ml.) whilstmaintaining the temperature in the range 0 to C. The resulting deepbrown solution was stirred for 30 minutes at room temperature and leftovernight.

The solvent was stripped off under reduced pressure and the solidobtained was extracted with ether. The solution was again evaporated toleave a solid which was dissolved in hot acetone, water mixture (3:1vol.) and refluxed for about 20 minutes. The solution or suspension wasconcentrated to small volume in vacuo and kept at 0 C. overnight. Thecrystalline mass Was filtered off, dried and extracted into ether. Theether was removed in vacuo and the solid recrystallised from carbontetrachloride, petroleum ether mixture (1 vol. to 2 vols.) to yield 2.6g. of colourless crystals, m.p. 151 C. It could be further purified byvacuum sublimation (at about 100-120 C./ 0.05 mm.).

EXAMPLE 11 2-(Benzo [b] thien-3-yl)-4,6-dichloro-s-triazine Benzo[b]thiophene (13.4 g., 0.10 mole) in dry benzene (20 ml.) was addeddropwise to a stirred solution of aluminium chloride (20 g., 0.15 mole)and cyanuric chloride (18.5 g., 0.10 mole) in benzene (200 ml.) andnitro- 12 methane (10 ml.). The dark mixture was heated at 40- 50 C. for4 hours then poured onto a mixture of ice (300 g.), concentratedhydrochloric acid (30 ml.) and ethyl acetate (300 ml.). The solventlayer was washed with water, dried over sodium sulphate and evaporatedto dryness under vacuum, to give a gum which was extracted with hotether. Evaporation of the ether extract and crystallisation of theresidue from acetone-water and then from dichloromethane-petroleumspirit gave pale crystals, m.p. 198-200 C.

EXAMPLE 12 2- [5'-(2"-Chlorothien-4"-yl) thien-2'-yl]-4,6-dichloro-s-triazine 2-Chlorothiophene (11.9 ml., 0.10 mole) in benzene(20 ml.) was added dropwise to a stirred solution of cyanuric chloride(9.5 g., 0.05 mole) and aluminium chloride (20 g., 0.15 mole) in benzene(200 ml.) and nitromethane (10 ml.). After stirring for 24 hours thedark mixture was poured onto a mixture of ice (300 g.) and conc.hydrochloric acid (30 ml.) and the mixture was extracted with ether. Theextract was evaporated to dryness under vacuum and the residue wascrystallised repeatedly from dioxane-water and from carbon tetrachlorideto give bright orange crystals, m.p. 200 C.

EXAMPLE 13 2-( l-Methylpyrrol-2-yl -4,6-dichloro-s-triazine Equimolarproportions of N-methyl pyrrole and cyanuric chloride were refluxed inbenzene overnight. The benzene was evaporated off and the productcrystallised from acetonitrile to yield2-(1-methylpyrrol-2'-yl)-4,6-dichloro-s-triazine, m.p. 157 C.yield 70%.Similarly other N-substituted pyrroles can be prepared.

EXAMPLE 14 2-(Thien-2'-yl)-4,6-dibromo-s-triazine The compound ofExample 10 (9.3 g., 0.04 mole) was refluxed for 5 hours in ethanol (200ml.) and concentrated hydrochloric acid (5 ml.). On cooling to roomtemperature, the 4,6-dioxo compound was precipitated in 100% yield.

The 2-(thien-2'-y1)4,6-diox0-s-triazine so obtained (2.93 g., 0.015mole) phosphorus tri'bromide (8.9 g., 0.033 mole) bromine (5.3 g., 0.033mole) and phosphoryl bromide (26 g., 0.090 mole) were well mixedtogether, and then heated with efiicient stirring under a watercondenser and a moisture guard tube. The mixture was quickly heated to80 C., then slowly heated up to C. over 1 hour, and finally maintainedat 120 C. for at least 5 hours.

The reddish-coloured liquid was allowed to cool down to about 50 C. andthen poured slowly into well stirred crushed ice (about 30 g.). Thewhole was vigorously stirred until the waxy mass of product had changedinto a discrete solid. The suspension was filtered at the pump and thesolid was dried in vacuo at room temperature in a dessicator.

The solid was purified by repeated crystallisations from a mixture ofcarbon tetrachloride and petroleum ether 60-80 C. (1:2 vol.); colourlesslong needles, m.p. 187 C., yield 0.45 g.

The identical product was obtained by carrying out the reaction ofExample 10 using cyanuric bromide.

EXAMPLE 15 By the methods described in Examples 5 to 13, cyanuricchloride was reacted with the appropriate heteroaromatic compound toproduce the following compounds:

2-( l'-isopropylpyrrol-2'-yl)-4,6-dichloro-s-triazine, m.p.

1 18-1 19 C. 2-(fur-2'-yl)-4,6-dichloro-s-triazine, m.p. 106 C.

2-(3'-methylthien-2-yl)-4,6-dichloro-s-triazine, m.p.

2-(5-ethylthien-2'-yl)-4,6-dich1oro-s-triazine, m.p. 67 C.

2-(4'-methylthien-2'-y1)-4,6-dichloro-s-triazine, m.p.

2-( 5 '-methoxythien-2'-yl -4,6-dichloro-s-triazine, m.p.

2-( l-ethylpyrrol-2'-yl -4,6-dichloro-s-triazine, m.p.

2-(5-methylfur- -yl)-4,6-dich1oro-s-triazine, m.p.

2-(5-acetylthien- -yl) -4,6-dichloro-s-triazine, m.p.

2-(3'-methoxythien-2'-yl)-4,6-dich1oro-s-triazine, m.p.

2-(1'-n-butylpyrro1-2'-y1)-4,6-dichloro-s-triazine, m.p.

2-(1'-phenylpyrro1-2'-yl)-4,6-dichloro-s-triazine, m.p.

2-( 1,5'-dimethylpyrrol-2-yl) -4,6-dichloro-s-triazine,

m.p. 170 C.

2-(1'-phenylindol-3'-yl)-4, 6-dichloro-s-triazine, m.p. 194-2-(1-benzylpyrrol-2'-yl)-4,6-dichloro-s-triazine, m.p.

2-(indol-3'-y1)-4,6-dichloro-s-triazine, m.p. 250252 C.

2-(5-methylpyrrol-2-yl) -4,6-dichloro-s-triazine, m.p.

In addition to the method described in Example 4, the compounds producedby the process of Examples 5 to 15 may also be nitrated as follows:

EXAMPLE 16 2 (4-Nitrothien-2'-yl) -4,6-dichloro-s-triazine2-(Thien-2'-yl)-4,6dichloro-s-triazine (5.75 g., 0.025 moles) was addedportionwise to a 4:1 volume mixture of concentrated sulphuric and nitricacids (25 ml.) keeping the temperature between 25 and 35 C. After theaddition, it was briefly heated to 50-60" C., then cooled, and carefullypoured on to crushed ice with stirring. After 1 hour, the product wasfiltered off and dried at 100 C. This product is2-(4'-nitrothien-2'-yl)-4,6-dioxo-s-triazine, m.p. 312-314 C. (dec.)after crystallisation from dimethylformamide.

It was chlorinated, using phosphorous pentachloride and phosphorousoxychloride, as in Example 1, to give the desired product, m.p. 186-187C. after recrystallisation from :1 volume hexanezchloroform mixture.

In the same manner 2-(5-ethyl-4'-nitrothien-2-yl)-4,6-dichloro-s-triazine, m.p. 150 C., was prepared.

EXAMPLE 17 2- l'-Methyl-4'-nitropyrrol-2-yl) -4,6-dichloro-s-triazine2-(1'-Methylpyrrol 2' yl) 4,6 dichloro s triazine (9.2 g., 0.04 mole)was hydrolysed to the dioxo-compound by refluxing for 5 hours withethanol (200 ml.) and concentrated hydrochloric acid (5 ml.). Thesolution was cooled to 0 C. and the product filtered off and dried.

This dioXo-compound (5.75 g., 0.03 mole) was added portionwise to amixture of water (10 ml.) conc. sulphuric acid (24 ml.) and conc. nitricacid (3.5 ml.) at a temperature of 25-30 C. with stirring. After afurther 45 minutes the mixture was tipped on to crushed ice, stirred for1 hour and the product filtered off and dried. This is 2-(1'-methyl-4-nitropyrrol-2'-yl -4,6-dioxo-s-triazine, m.p. 3 3 1- 332 C.after crystallisation from dimethylformamide.

Chlorination, as in Example 1, gave the desired 4,6- dichloro-compound,m.p. 179 C. after several recrystallisations from a 10:1 volume mixtureof hexane and chloroform.

Similarly 2 (5-nitrofur-2-yl)-4,6-dichloro-s-triazine, m.p. 166-168 C.,was prepared.

The following Examples illustrate formulations containing an activeingredient of formula 1:

EXAMPLE 18 In use, this wettable powder concentrate is diluted withwater to form a spray composition containing from 400 to 800 p.p.m. ofactive ingredient.

EXAMPLE 19 A wettable powder containing the following ingredients wasprepared:

Percent by weight 2-(1'-phenylpyrrol-2'-yl)-4,6-dich1oro-s-triazineDioctyl ester of sodium sulphosuccinic acidanionic surfactant 10 Kaolin10 In use, this powder is dispersed in water to form a spray compositioncontaining from 600 to 1000 p.p.m. of active ingredient.

EXAMPLE 20 An emulsifiable concentrate containing the followingingredients was prepared:

Percent by weight 2-(4'-methylthien- -yl)-4,6-dichloro-s-triazine 20Sodium alkyl aryl sulphonate blendemulsifier 6 Polyoxyethylene sorbitanmonolauratenonionic emulsifier 5 Xylene 69 This composition is dilutedprior to use with water to form a sprayable emulsion containing from 200to 600 p.p.m. of active ingredient.

We claim:

1. The method of treating plants susceptible to attack by plantpathogenic fungi which comprises applying to said plants a fungicidallyeffective amount of a compound of the formula wherein X is halogen and Ris a monoor bi-cyclic heteroaromatic group linked through a carbon atomto the triazine ring, said group being selected from the groupconsisting of wherein R is hydrogen, C -C alkyl, vinyl, allyl,hydroxymethyl, hydroxyethyl, carboxymethyl, carboxyethyl, phenyl, benzylor phenethyl and R is hydrogen, C -C alkyl, C -C alkoxy, C -C acyl,phenyl, nitro, amino, chlorine or bromine.

2. The method of claim 1 wherein X is chlorine or bromine and R isselected from the group consisting of wherein acyl, phenyl, nitro,amino, chlorine or bromine. 15 3,259, 3. The method of claim 1, whereinX is chlorine or 2,322,313 bromine and R is selected from the groupconsisting of 2,880,207 2,953,564

o N 1k, 1;.

R is hydrogen, C -C alkyl, C -C alkoxy, C -C acyl,

phenyl, nitro, amino, chlorine or bromine, and R is hydrogen, C -Calkyl, vinyl, allyl, hydroxymethyl, 5 hydroxyethyl, carboxymethyl,carboxyethyl, phenyl,

benzyl or phenethyl. 4. The method of claim 3, wherein said compound isa 2-( 1-alkylpyrrol-2'-yl)-4,6-dichloro-s-triazine.

5. The method of claim 4, wherein said compound is 2-(1'-methylpyrrol-2'-yl) -4,6-dichloro-s-triazine.

References Cited UNITED STATES PATENTS Duennenberger et al. 424-60 XALBERT T. MEYERS, Primary Examiner L. SCHENKMAN, Assistant Examiner mgUm'mn STATES PATENT @FFICE CERTIFEQATE OF CO EQTIGN Patent No. 5, 5 ,9 5Dated August ,20, 196 2- Inventofls) Jiban Kumar Chekrebarti and AlecTodd It is certified cheterror appears in the above-identified patentand that said Letters Patent are hereby corrected as shown below:

r In column 25 line 16, "ingredients" should read --ingred ient-- Incolumn 2, line 56, "or"fshould read -'--of-@ In column 5, line ll,should read i l o N H should read In column 5, line 18,

. -K $1 I! Cali-L0 In column 5, line +6, "8." should not be in italics.

In column 7, line 6 "-dichlor should read -dichloro- In column 8, line15, 'after the compound "2-(5'- ethylbenzo[b]thien5-yl)-+,6-dichloro-s-triazine", the following two compounds should appear: 2-=(benzo[b]fur-2 -yl)-h,6- dichloro s-triazine and 2- (l -benzylindol5=-yl)- l,6- dichloro-s -trie.zine

In column 10, line 505 "-2-" should read. -2'

Signed and sealed this 28th day of January 1975.

(SEAL) Attest:

MCCOY M. GIBSON JR. C. MARSHALL DANN Attesting Officer V Copm l slonerof Patents.v

